Regulatory and Reimbursement HarmonizationAn Industry PerspectiveAdrian Griffin | April 2016

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One Global Development PlanMany geographies, More Stakeholders

Discovery3 yrs

Early Development

2 yrs

Phase II2 yrs

Phase III3 yrs

Regulatory review 1-2yrs

Launch

Need to know evidence requirements 4-7 yrs before launch

InitialPlan

EvidencePlan

‘Locked’

ClinicalUse

Planning the Evidence - Predicting the future

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Need for Regulatory and HTA Agencies to be Aligned

Focus of HTAi Policy Forum, 2011

International Journal of Technology Assessment in Health Care, 27:3 (2011), Page 1 of 8.

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Different Focus, Different DecisionsBoth driving for better outcomes for patients

Regulation HTA Coverage

Role Give market authorisation

Support for clinical and coverage decisions

Decide on coverage or reimbursement

DecisionDo the clinical benefits for patients outweigh the risks?

[HTA supports decisions, often taking into account clinical, financial & other dimensions]

Are the expected health benefits useful and affordable?

EvidenceEfficacy and safety from trials; post launch surveillance

Effectiveness, cost effectiveness and opportunity costs from trials, other studies and modelling

As for HTA; conditional coverage may be used to improve evidence base for re-appraisal

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Regulatory-HTA Interactions have been Increasing

Timing

• Pre-competitive

• During Development– Pre-Phase II / III

• Pre-Market / launch

Type of Interaction

• Disease Specific – Evidence Guidance Documents

• Green Park Collaborative

• Early Scientific Advice– Product specific advice– HTA, Multi-HTA, Parallel Reg-HTA

• Parallel reviews– Regulatory and reimbursement

• Canada, Australia, US

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• Regulator, patient, clinicians call for ‘early access’

– FDA: Breakthrough therapies– EMA: PRIME

• Regulators discussing longitudinal approach to approval

– “Adaptive Licensing”Now Medicines Adaptive Pathways to Patients (MAPPs)

• How will HTA & Reimbursement adapt?– Existing approach to value assessment

needs to evolve

New Challenges for Stakeholders

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Ibrutinib versus Ofatumumab in previously treated CLL: Byrd et al, NEJM, July 2014

The Challenges are here now

Crossover bias

Ofatumumab as single agent CD20 immunotherapy in fludarabine-refractory CLL: Wierda et al, JCO, April 2010

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Ongoing Initiatives

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Ongoing Initiatives (2)

To show how Real World Evidence (RWE) can be adopted

in to medicine development & decision making, and provide the

tools to achieve it

https://www.imi-getreal.eu/

An enabling platform to coordinate MAPPs activities.

Supporting evidence generation, designing the MAPPs pathway, decision-making & sustainability

http://adaptsmart.eu/

Both are multi-stakeholder, including regulators, HTA agencies, patient organisations, academics and industry

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Countries can find ways to deliver access, whilst managing their uncertainty

Scheme type

Rebate for early non-responders

Capped treatment duration

Treatment duration linked rebate

Response scheme

Initiation period costs

Population level cap

Range of Managed Entry Agreement Archetypes in use in Europe, for One Drug in one Disease

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Challenges

• Regulators are Decision-Makers– Able to change their decision-making paradigm

• HTA-agencies provide information & recommendations– Third parties then make Reimbursement decisions

• What flexibility do HTA-agencies have to navigate the reimbursement access model?

– Will a new model be required in the new regulatory environment

• Industry needs to address Regulators, HTAs, Clinicians and Patients